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Article
Open AccessEvolutionary trade-offs associated with loss of PmrB function in host-adapted Pseudomonas aeruginosa
Pseudomonas aeruginosa colonises the upper airway of cystic fibrosis (CF) patients, providing a reservoir of host-adapted genotypes that subsequently establish chronic lung infection. We previously experimentally...
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Protocol
EpiSweep: Computationally Driven Reengineering of Therapeutic Proteins to Reduce Immunogenicity While Maintaining Function
Therapeutic proteins are yielding ever more advanced and efficacious new drugs, but the biological origins of these highly effective therapeutics render them subject to immune surveillance within the patient’s...
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Article
Discovery of novel S. aureus autolysins and molecular engineering to enhance bacteriolytic activity
Staphylococcus aureus is a dangerous bacterial pathogen whose clinical impact has been amplified by the emergence and rapid spread of antibiotic resistance. In the search for more effecti...
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Article
Computationally driven deletion of broadly distributed T cell epitopes in a biotherapeutic candidate
Biotherapeutics are subject to immune surveillance within the body, and anti-biotherapeutic immune responses can compromise drug efficacy and patient safety. Initial development of targeted antidrug immune me...
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Chapter and Conference Paper
Structure-Guided Deimmunization of Therapeutic Proteins
Therapeutic proteins continue to yield revolutionary new treatments for a growing spectrum of human disease, but the development of these powerful drugs requires solving a unique set of challenges. For instanc...
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Chapter and Conference Paper
Optimization of Combinatorial Mutagenesis
Protein engineering by combinatorial site-directed mutagenesis evaluates a portion of the sequence space near a target protein, seeking variants with improved properties (stability, activity, immunogenicity, e...
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Article
Open AccessOptimization algorithms for functional deimmunization of therapeutic proteins
To develop protein therapeutics from exogenous sources, it is necessary to mitigate the risks of eliciting an anti-biotherapeutic immune response. A key aspect of the response is the recognition and surface di...
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Article
Open AccessQuantifying and resolving multiple vector transformants in S. cerevisiae plasmid libraries
In addition to providing the molecular machinery for transcription and translation, recombinant microbial expression hosts maintain the critical genotype-phenotype link that is essential for high throughput sc...
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Chapter and Conference Paper
Protein Fragment Swap**: A Method for Asymmetric, Selective Site-Directed Recombination
This paper presents a new approach to site-directed recombination, swap** combinations of selected discontiguous fragments from a source protein in place of corresponding fragments of a target protein. By be...
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Protocol
pH Sensing Agar Plate Assays for Esterolytic Enzyme Activity
Lipases and esterases are some of the most extensively used enzymes for biotransformations (1–3). This is in part due to their widely applicable chemistry, often exceptional regio- and stereo-selectivity, lack of...
